- Understanding the capacity of the cellular immune response to clear Borrelia, the etiologic agent of Lyme disease, is essential to a proper understanding of the pathogenesis of this disorder. We know that both neutrophils and macrophages take up and kill Borrelia rapidly in vitro. Yet, intact spirochetes can be observed in skin and other tissues, and have been isolated from uninflamed peritoneal cavity despite the presence of resident macrophages. In order to examine the failure of phagocytes to clear the spirochetes in vivo, the killing mechanisms of phagocytes will be characterized. In situ microscopic examination of spirochete- phagocyte interactions, in situ hybridization and ex vivo RT-PCR of cytokine and other genes will be used to establish a profile of the macrophages' state of activation and deactivation. Different strains of Borrelia will be used to elucidate mechanisms of clearance versus persistence in vivo. Finally, it is proposed to use cDNA arrays to examine differences in host gene expression patterns during activation of neutrophils and macrophages by these types of Borrelia. These studies may provide the technical and conceptual basis for improvements in diagnostic and prognostic aspects of inflammatory diseases.